tbuckley/cabot-search huggingface dataset:
Abstract 15578: A Rare Case of Anomalous Left Main Coronary Artery Origin Presenting as ST Elevation Myocardial Infarction
Authors: Patrick Zakka, Vaughn Eyvazian, Ramin Assadi
Journal: Circulation (2022)

Background: ST-segment elevation myocardial infarctions (STEMI) are uncommon presentations of coronary artery anomalies and pose challenges in the emergent setting of percutaneous coronary interventions. We describe an extremely rare case of left main coronary artery (LMCA) originating off the right coronary artery (RCA) in a patient who presents with STEMI and was found to have Medina 1,1,1 lesion at the origin of the anomalous (LMCA). Case Presentation: An 81-year old male, with a past medical history significant for aortic stenosis and hyperlipidemia, presents to the emergency room for substernal non-radiating chest pressure. His electrocardiogram showed ST segment elevations in inferior and anterior leads. He was taken emergently to the cardiac cath lab. Coronary angiogram revealed a single right coronary ostium with an anomalous LMCA to mid left anterior descending (LAD) artery via dual insertion within a myocardial bridge. There was severe 90% Medina 1,1,1 bifurcating proximal RCA stenosis and 90% proximal LMCA stenosis. The entire left coronary system was fed by the anomalous LMCA, which was inserted into the mid-LAD in a dual insertion, between which there was a myocardial bridge. Cardiothoracic surgery team was consulted, and decision was made to pursue coronary artery bypass grafting (CABG). An intra-aortic balloon pump was placed via right femoral artery and patient was taken for emergent surgery, where he underwent 3 vessel CABG (left internal mammary artery to LAD, saphenous venous graft to obtuse marginal branch and posterior descending artery). Discussion: A broad spectrum of coronary anomalies have been reported, but their incidence in STEMI is rare. We discuss a very rare anomaly in which the entire left coronary system branches off the RCA, and culprit lesion was found to be a Medina 1,1,1 lesion. We aim to add to the sparce data pool of STEMI management in patients with anomalous coronary arteries.
Abstract 161: Impact Of Leukocyte Filtration And Leukocyte Modulation On Myocardial Injury After Prolonged Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation In A Swine Model
Authors: Takahiro Nakashima, Jinhui Liao, Jensyn VanZalen, Annie Phillips, Joseph Hill, Stephen Harvey, Keenan Longan, Angela Westover, Liandi Lou, HARVEY D HUMES, Robert Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2022)

Background: Post-arrest myocardial dysfunction is one of the major causes of rearrest within early period after return of spontaneous circulation (ROSC). Multiple interacting processes including leukocyte-mediated injury is suspected to contribute to deterioration of cardiac function after cardiac arrest. Unlike the standard leukocyte filter (LF), the leukocyte modulation (L-MOD) device is expected to alter the natural inflammatory process by preferentially binding and inactivating the activated leukocytes. We tested the hypothesis that either a standard LF system or a L-MOD device will decrease myocardial injury during extracorporeal cardiopulmonary resuscitation (ECPR). Methods: Total 34 swine (45.5±2.5 kg, male=18, female=16) underwent 8 minutes of untreated ventricular fibrillation cardiac arrest followed by mechanical CPR for 30 minutes. Immediately followed by 8 hours of ECPR with randomly assigned leukocyte treatment protocol; ECPR with standard care (n=10), LF (n=12), and L-MOD (n=12). Left ventricular ejection fraction (LVEF) was evaluated hourly by transthoracic echocardiography. At the end of the study, the heart was removed, fixed and embedded in paraffin. 5- μm sections off the left and right ventricular (RV) free wall were H &amp; E stained for analysis. Five views each of LV and RV under 20хobjective lens were randomly selected with Leica LAS X software. Myofiber degeneration and hemorrhage were graded as 0 (absence) to 3 (severe). Grade was average of 5 views. Results: The mean LVEF at baseline was 65±6%. There were no significantly difference in rate of achieving ROSC (70% vs. 75% vs. 58.3%, p=0.671) and LVEF at 8 hours after initiating ECPR (35±27% vs. 36±31% vs. 28±30%, p=0.776) between the group with control, LF, and LMOD respectively. There were no significant difference in myofiber degeneration grade (LV, 1.5±0.5 vs. 1.1±0.6 vs. 1.4±0.4, p=0.334; and RV, 1.6±0.6 vs. 1.8±0.7 vs. 1.5±0.6, p=0.525) and hemorrhage grade (LV, 0.0±0.1 vs. 0.0±0.1 vs. 0.0±0.1, p=0.841; and RV, 0.0±0.0 vs. 0.0±0.0 vs. 0.0±0.0) between control, LF, and L-MOD groups. Discussion: In swine model with prolonged cardiac arrest treated with ECPR, a standard LF system and a L-MOD device did not decrease early myocardial injury.
Abstract 15451: Using Fitbit Measured Activity Levels as an Indicator of New York Heart Association (nyha) Functional Class
Authors: Zhengxin Tang, Ben Gerber, Susan J Pressler, Jinsong Chen, Susan Buchholz, Mayank M Kansal, Todd Ruppar, JASMINE ARRINGTON, Ayomide Owoyemi, Jonathan Leigh, Spyros Kitsiou
Journal: Circulation (2022)

Introduction: Commercially available wearable devices for physical activity (PA) monitoring may provide objective data to facilitate assessment of NYHA class in patients with heart failure (HF). However, there is limited research exploring their ability to differentiate patients between NYHA classes. Objective: This study aims to assess the relationship between NYHA class and PA using a Fitbit wrist-based activity tracker (Charge 3) in patients with HF. Methods: We conducted a secondary analysis of baseline NYHA and PA data (daily step count and minutes of moderate-to-vigorous PA [MVPA]) collected by the iCardia4HF trial, which examined the feasibility and preliminary efficacy of a mHealth intervention for HF self-care. NYHA class was determined by a trained research assistant at the baseline visit, using standardized criteria. Daily steps and MVPA minutes were measured using Fitbit data from the first 7 days after the baseline visit. To be included in the analysis, patients had to have ≥4 days with ≥600 minutes of Fitbit wear-time/day. Results: We analyzed data from 78 participants (mean age=55.2 years [SD 10.6]; female=43.6%; Black/African American= 79.5%; mean BMI=35.6 kg/m2 [SD 8.7]; HFrEF=65.4%). The Kruskal-Wallis test demonstrated significant differences in the distribution of daily steps (p=.021) and MVPA (p=.023) across NYHA classes. Pairwise comparisons showed that patients in NYHA Class III had significantly lower daily steps and MVPA minutes than patients in Class I. There were also important differences in daily steps and MVPA between patients in NYHA Class III and II, and Class II and I, but these did not reach statistical significance. Conclusions: There was a general decrease in steps and MVPA duration with increasing NYHA class. Wrist-worn activity trackers represent a promising method for estimating NYHA class and assessing HF severity and progression through continuous PA monitoring, but larger studies are needed for validation.
Abstract 15670: Clinical Relevance of a Polygenic Susceptibility to Dilated Cardiomyopathy
Authors: Liam Gaziano, Kiran Biddinger, Sean J Jurgens, Seung H Choi, Steven A Lubitz, Patrick T Ellinor, Krishna Aragam
Journal: Circulation (2022)

Introduction: Both rare and common genetic variants have been associated with dilated cardiomyopathy (DCM), but their contributions to DCM risk in the context of clinical factors remains unexplored. Methods: In the UK Biobank, we identified carriers of rare, monogenic variants of relevance to DCM (ClinGenLOF), and also computed a genome-wide, common-variant (polygenic) score (GPS) based on imaging-derived measures of left ventricular structure and function. We evaluated the contributions of ClinGenLOF status, the GPS, and clinical factors to incident DCM through measures of relative risk, phenotypic variance explained (i.e. population attributable fraction, PAF), and discrimination. Results: In 160,485 UK Biobank participants, mean age was 56.5 (SD 8.1), 89,888 (56%) were female, and 226 developed DCM during a median of 10.9 years of follow-up. ClinGenLOF carriers had the highest hazards of disease (HR=14.5, 95%CI: 9.43 to 22.11), followed by atrial fibrillation (HR=3.25, 95%CI:1.94 to 5.48), and chronic kidney disease (2.56 95%CI:0.81 to 8.12). In contrast, hypertension accounted for the greatest proportion of DCM risk in the population (PAF=23.2%) followed by having a high (&gt;80th percentile) polygenic score (PAF= 17.9%). On top of a reference model, improvements in discrimination were individually greatest with addition of ClinGenLOF status (delta C-index = 0.049) or the GPS (delta C-index = 0.031), comparable to the addition of all clinical factors combined (delta C-index = 0.032; Figure ). When added sequentially to a model inclusive of clinical factors, ClinGenLOF status (delta C-index = 0.046) and GPS (additional delta C-index = 0.021) further improved discrimination. Conclusions: Rare, monogenic variants, a polygenic score, and clinical factors all contribute substantially to risk of DCM. Considering cumulative genetic (monogenic and polygenic) risk on top of clinical factors improves the prediction of incident DCM in the general population.
Abstract 211: Epinephrine Does Not Correct Post-ROSC Hypoperfusion Despite Normalizing Blood Pressure A Rat Model Of Severe Pediatric Asphyxial Cardiac Arrest
Authors: Hoai Ton, Victor Velado, Michael Shoykhet
Journal: Circulation (2022)

In children resuscitated from cardiac arrest, systemic hypotension occurs frequently and is associated with worse outcome. The first-line vasoactive treatment for post-arrest hypotension is continuous infusion of epinephrine. Epinephrine dose is titrated to maintain normal blood pressure for age. Epinephrine, however, also leads to vasoconstriction which may impair organ perfusion after resuscitation.We hypothesized that epinephrine infusion during the post-resuscitation period restores systemic blood pressure but not flow to vital organs. Using a model of severe pediatric asphyxial cardiac arrest in developing rats, we simultaneously measured blood pressure (ABP) and flow in carotid (Fc) and femoral (Ff) arteries after resuscitation. We then compared the effects of epinephrine or saline infusions on blood pressure vs flow. One hour after resuscitation from 11.5 minutes of asphyxial arrest, ABP, Fc and Ff were 61.73 ± 2.68; 42.58 ± 3.84; and 19.53 ± 7.00 % of baseline. Epinephrine infusion increased ABP in a dose-dependent manner, reaching 95.13 ± 7.93 % of baseline at 0.5 μg/kg/min. Saline infusion at equivalent volumes increased ABP only marginally to 69.88 ± 2.60 % of baseline. In contrast to its effect on ABP, epinephrine infusion increased Fc only to 49.55 ± 6.49 and Ff to 53.28 ± 7.13 % of baseline. Saline infusion at equivalent volumes, on the other hand, had a more salutary effect than epinephrine on improving blood flow (Fc 64.62 ± 6.64 and Ff 60.25 ± 7.60 % of baseline). Notably, a single 10 cc/kg saline bolus, administered when ABP decreased to ~80% of baseline post-ROSC, increased blood flow and ABP to 100% and 90% of baseline, respectively. These data indicate that epinephrine infusion in the post-arrest period adversely affects arterial blood flow despite normalizing arterial blood pressure. Continued fluid resuscitation with crystalloids potentially has beneficial effect on correcting post-ROSC hypoperfusion. Future studies need to explore the impact of targeting flow rather than blood pressure in the post-arrest period and its association to post-arrest end-organ function in children.
Abstract 15832: Optogenetic Stimulation of Intrinsic Cardiac Autonomic Neurons Reveals the Interaction Between Catecholaminergic and Cholinergic Pathways
Authors: Rebekah D Russo, Angel R Moreno, David Mendelowitz, Matthew W Kay
Journal: Circulation (2022)

Autonomic tone, through the interaction of catecholaminergic and cholinergic pathways, is a powerful modulator of cardiac function. Until recently, selective activation of cardiac autonomic pathways has required administration of exogeneous neurotransmitters or careful placement of electrodes to stimulate specific neural populations. Optogenetics enables broader exploration of autonomic interactions through the selective expression of channelrhodopsin (ChR2) in neural populations. Our objective was to simultaneously activate catecholaminergic and cholinergic pathways, by exogenous perfusion of neurotransmitter and photostimulation of opposing autonomic neurons, to test the hypothesis that simultaneous activation will reveal the fast kinetics of cholinergic modulation of catecholaminergic increases in heart rate (HR). Norepinephrine (NE) and acetylcholine (ACh) were administered to perfused transgenic mouse hearts that expressed ChR2 within sympathetic tyrosine hydroxylase neurons (TH+ChR2) or parasympathetic choline acetyltransferase (ChAT+ChR2) neurons. Intrinsic neurons were photostimulated by illuminating the SA node with a 465nm high power microLED. The ECG was recorded to measure beat-to-beat changes in HR. Moderate doses of exogeneous NE increased HR 26.77±5.61% (n=3) and high doses increased HR 59.74±8.77% (n=3). At all NE doses, photostimulation of ChAT+ChR2 neurons immediately reduced HR to values equivalent to, or lower than, pre-NE HR. Arrhythmias were not observed. In companion studies, moderate doses of exogeneous ACh reduced HR 19.98±4.68% (n=7) and high doses reduced HR 51.31±4.07% (n=7). HR increases caused by TH+ChR2 neuron photostimulation were diminished by exogenous ACh in a dose-dependent manner. Increased dosing of exogeneous ACh, with simultaneous TH+ChR2 neuron photostimulation, dramatically shortened the onset of 2 nd degree AV block and increased its severity. At high concentrations of exogeneous ACh, non-sustained arrhythmias were observed upon the cessation of TH+ChR2 neuron photostimulation. These results provide new insight into the kinetics of intrinsic cardiac autonomic interactions and reveal powerful modulation of catecholaminergic activity by cholinergic activation.
Abstract 15469: Activation of Sting Pathway Promotes Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Wall
Authors: Abhijit Chakraborty, Yanming Li, Chen Zhang, Yang Li, Kimberly Rebello, Lin Zhang, Kaifu Chen, Hernan Vasquez, Joseph S Coselli, Scott A LeMaire, Ying H Shen
Journal: Circulation (2022)

Introduction: Smooth muscle cell phenotypic alteration is a prominent feature of aortic aneurysms and dissections (AAD) that causes the loss of functional, contractile, smooth muscle cells (SMCs) and subsequent aortic dysfunction. However, SMC phenotypic alteration in AAD and the underlying mechanism is poorly understood. Hypothesis: Stress on the aorta induces a phenotypic switch in SMCs from a contractile role to a pro-inflammatory role that promotes cell dysfunction and death. Methods: We performed single-cell RNA and ATAC sequencing (scRNA-seq, scATAC-seq) of ascending aortic tissues from patients with sporadic ascending AAD and organ donor controls, alongside murine aortic tissues from a sporadic AAD model and wild-type mice. The role of the STING pathway in SMC phenotypic alterations was studied in human aortic SMCs. Chromatin immunoprecipitation assays were used to study epigenetic regulation Results: Significant SMC transformation from a contractile phenotype to a pro-inflammatory, pro-fibroblast, and pro-death phenotype was seen in scRNA-seq of aortic tissues from AAD patients and a sporadic AAD murine tissue. Our sc-ATACseq indicated that SMC transformation was partially controlled by chromatin remodeling of these genes, and IRF3 was identified as a key transcriptional factor for the reduction of chromatin accessibility of contractile genes, but induction of chromatin accessibility of inflammatory genes. In cultured SMCs, cytosolic DNA, through STING-TBK1 signaling, activated IRF3, which directly bound cis-elements of contractile genes, and recruited EZH2 to induce repressive H3K27me3 modification, leading to SMC gene suppression. Activated IRF3 also induced inflammatory gene expression. SMC-Sting deficiency prevented proinflammatory phenotypic switch in the sporadic AAD mouse model and restored contractile phenotype. Conclusion: We highlight an epigenetic pathway responsible for SMC dysfunction that induced SMC gene suppression and SMC phenotype changes and identified STING-TBK-IRF3-EZH2 as key signaling that suppresses SMC genes. To the best of our knowledge, this is the first study reporting that the STING pathway contributes to AAD development by SMC transition from a contractile to an inflammatory phenotype.
Abstract 167: Nasal Sensor Capnographic Differences In Major Traumatic Brain Injury Patients Receiving Non-rebreather Mask Versus Nasal Cannula Oxygen Delivery
Authors: Bruce J Barnhart, Daniel W Spaite, Dawn B Jorgenson, Adam Seiver, Eric D Helfenbein, Joshua B Gaither, Amber D Rice, Samuel M Keim, Chengcheng Hu
Journal: Circulation (2022)

Background: The advent of highly sensitive End-Tidal CO2 (ETCO2) sensors allows effective monitoring of intubated patients in EMS. Previous work has explored the use of ETCO2 monitoring in non-intubated patients with sensors placed in the nares. However, little is known about the effect of passive O2 delivery [nasal cannula (NC) or high-flow, non-rebreather mask (NRB)] on ETCO2 measurement. Objective: To compare ETCO2 measurements in non-intubated Traumatic Brain Injury (TBI) patients receiving O2 via NC vs. NRB in the field. Methods: A subset of cases from the EPIC EMS TBI Study (NIH-1R01NS071049) were evaluated (4/13-4/18). Non-intubated cases from 5 EMS agencies providing monitor data, including continuous ETCO2. Start and end segments were excluded to remove artifact from initiation (“ramp-up”) or termination of monitoring. Statistics: Wilcoxon rank-sum test, two-sample t-test, and Chi-squared test were used as appropriate. Linear regression compared continuous variables in adjusted analyses (α = 0.05). Results: Included were 151 cases [median age: 52 (range: 9-91; 66% male)]. Of those, 62 (41%) received NCO2 and 89 (59%) via NRB. Patient-level mean ETCO2 was slightly lower in the NC group (mean = 26.9 mmHg; SD 6.7) compared to NRB (mean 30.2; SD 8.1; p=0.007). Differences in the mean were: Unadjusted: 3.3 (95% CI 0.9-5.7); Adjusted 2.7 (0.2-5.2). There were no significant differences in means of the patient-level lowest or highest recorded values. Conclusion: While there was a statistically lower ETCO2 in the NC versus NRB-oxygenated patients, it was around 3 mmHg and, thus, not clinically significant. This is surprising since: 1) the O2 flow rates and 2) the open-air (NC) versus mask (NRB) delivery methods are so dramatically different. Future study is needed to identify the clinical implications of using noninvasive ETCO2 measurement as a tool for monitoring ventilatory status and changes in non-intubated TBI (and other) patients in emergency settings.
Abstract 163: Lung Inflation Occurs Infrequently In Most Patients During 30:2 CPR With Bag-Valve-Mask Ventilation
Authors: Ahamed H Idris, Elisabete Aramendi, Brian Leroux, Xabier Jaureguibeitia, Sarah Shaver, Peter J Kudenchuk, Thomas Rea, Jim Christenson, Mary Chang, Christian Vaillancourt, Jennifer E Blackwood, David D Salcido, Clifton W Callaway, Pamela Owens, Henry Wang
Journal: Circulation (2022)

Background: Few studies have measured ventilation early in cardiopulmonary resuscitation (CPR) before advanced airway placement. In 30:2 CPR, there is a pause to give two ventilations after each round of 30 chest compressions. Recently, we developed a method to identify lung inflation (ventilation) waveforms from thoracic bioimpedance defibrillator recordings measured through defibrillator pads. Early work showed that in 75% of patients receiving bag-valve-mask (BVM) ventilation, lung inflation waveforms occurred in less than half of pauses in chest compressions during 30:2 CPR. Objective: To determine the incidence of lung inflation with BVM during 30:2 CPR in a multi-center study. Methods: Our study included adult out-of-hospital cardiac arrest patients from five sites of the Resuscitation Outcomes Consortium Trial of Continuous or Interrupted Chest Compressions during CPR. Patients had 30:2 CPR with ≥ two minutes of thoracic bioimpedance signal recorded with a defibrillator (Lifepak, Physio-control, Redmond, WA or MRx, Philips, Andover, MA). Previously, we defined a ventilation waveform as having a bioimpedance amplitude ≥0.5 Ohm (corresponding to ≥ 250 ml Vt) with a duration ≥1 sec. A valid pause was 3 sec to 15 sec. An automated program analyzed the recordings. We describe groups with ventilation waveforms in &lt;50% or ≥50% of pauses. Results: We included 1,552 patients; mean age was 66 years, 67% were male, mean (±SD) duration of 30:2 CPR was 9.9 ±5.8 min from the start of chest compressions until advanced airway placement. During this period there was a total of 21,705 pauses in chest compressions, a median of 12 pauses in chest compressions, and a median of 5 ventilations; 56% of patients had ventilation waveforms in &lt;50% of pauses (Group 1, N=868), and 44% had waveforms in &gt; 50% of pauses (Group 2, N=678). The median (IQR) number of pauses in Group 1 vs. Group 2, was 12 (8, 20) vs. 12 (7, 17) and the median number of ventilations was 3 (1, 6) vs. 13 (7, 21), respectively, during 30:2 CPR. The median duration of pauses for Group 1 vs. Group 2, was 5.8s (5.0, 6.5) vs. 5.7s (5.0, 6.7). Conclusion: For most patients, this multi-center study showed that ventilation waveforms were present in less than 50% of pauses in chest compressions during 30:2 CPR with BVM ventilation.
Abstract 15836: Time Trends in Infectious and Chronic Disease Consultations in Dakar, Senegal: Impact of Covid-19 Preventative Measures
Authors: Massamba Diop, Bamba Gaye, Ibrahima Bara Diop, Crystal N Cene, Xavier Jouven
Journal: Circulation (2022)

Background: The impact of COVID-19 preventative measures (use of face masks, social distancing, quarantines, and sanitation and hygiene practices) on the time trends in infectious and chronic disease consultations in Sub-Saharan Africa remains unknown. Methods: We conducted a cohort study on all emergency medical consultations over a five-year period, January 2016 to July 2020, from SOS Medecins in Dakar, Senegal. The consultation records provided basic demographic information such as age, ethnicity (Senegalese v. Caucasian), and sex as well as the principal diagnosis using an ICD-10 classification (‘infectious, ‘chronic’, and ‘other’). Firstly, we investigated how the pattern in emergency consultation differed from March to July 2020 compared to previous years. Secondly, we examined any potential racial/ethnic disparities in COVID-19 consultation. Findings: Data on emergency medical consultations were obtained from 53,583 patients of all ethnic origins. The mean age of patients was 37·0 ± 25·2 and 30·3 ± 21·7 in 2016-2019 and 45·5 ± 24·7 and 39·5 ± 23·3 in 2020 for Senegalese and Caucasians. The type of consultations between the months of January and July were similar from 2016 and 2019; however, in 2020, there was a drop among the numbers of infectious disease consultations, particularly from April to May 2020 when sanitary measures for COVID-19 were applied (average of 366·5 and 358·25 in 2016-1019 and 133 and 125 in 2020). The prevalence of chronic conditions remained steady during the same period (average of 381 and 394·75 in 2016-2019 and 373 and 367 in 2020). In a multivariate analysis after adjusting to age and sex, infectious disease consultations were significantly more likely to occur in 2016-2019 compared to 2020 (OR for 2016= 2·39, 2017= 2·74, 2018= 2·39, 2019= 2·01). Furthermore, the trend in the number of infectious and chronic consultations were similar among Senegalese and Caucasian groups, indicating no disparities among those seeking treatment. Conclusion: During the implementation of COVID-19 preventative measures, infectious disease rates dropped as chronic disease rates stayed stagnant in Dakar. Furthermore, no racial/ethnic disparities were observed among the infectious and chronic consultations.